Over the past decade, improvements in mass spectrometry (MS) have allowed MS to take a place among standard analytical tools in the study of biologically relevant macromolecules, notably proteins purified from complex biological systems. For example, the development of matrix-assisted laser desorption/ionization approaches has permitted MS analysis to be applied to large molecular weight analytes, including proteins as large as several hundred kilodaltons, while affinity capture laser desorption/ionization approaches have made possible the selective concentration from inhomogeneous samples of desired analytes directly on active surfaces of the sample probes. Improvements in hardware, including control and detection electronics, have led to improved sensitivity, mass accuracy and resolution, while improved software algorithms have improved the ability to use the data so obtained to identify unknown analytes.
In affinity capture laser desorption/ionization, the active surfaces of the laser desorption/ionization probe are affinity capture surfaces, which are capable of adsorbing analytes selectively from heterogeneous samples, concentrating them on the probe surface in a form suitable for subsequent laser desorption/ionization. The probes then are used to deliver the samples into a mass spectrometer for interrogation by a laser source. Optionally, energy-absorbing (or “matrix”) molecules are applied prior to analysis.
Affinity capture surfaces of affinity capture laser desorption/ionization probes can include either a chromatographic or a biomolecule affinity moiety. Chromatographic affinity surfaces have an adsorbent capable of chromatographic discrimination among or separation of analytes. Such surfaces can thus include anion exchange moieties, cation exchange moieties, reverse phase moieties, metal affinity capture moieties, and mixed-mode adsorbents, as such terms are understood in the chromatographic arts. Biomolecule affinity surfaces have an adsorbent comprising biomolecules capable of specific binding. Such surfaces can thus include antibodies, receptors, nucleic acids, lectins, enzymes, biotin, avidin, streptavidin, Staph protein A and Staph protein G.
Liquid samples typically applied to the active surfaces of laser desorption/ionization probes, including affinity capture laser desorption/ionization probes, are typically several microliters in volume; after subsequent purification processes, usually only picomoles to nanomoles of analytes remain for analysis in the mass spectrometer.
With such small quantities of analytes, and with spectrometers having such high sensitivity, contamination of the active surfaces is a major problem in use of probes. Specifically, when an operator handles and transfers the probes, there are numerous opportunities for the operator inadvertently to grasp the probes on or near one or more of its active surfaces (such as affinity capture surfaces)—and consequently, to contaminate the samples thereon with finger proteins, such as collagen, and dirt. For example, an operator is presently called upon to handle each probe at least three times during the analysis process, providing at least three opportunities to contaminate each probe: once to transfer the probe from a shipping container to a sample preparation platform, once to transfer the probe from the sample preparation platform to a mass spectrometer, and once to transfer the probe to storage. Each successive contact with the probe increases the likelihood of accidental contamination of the active surfaces, and consequent interference with analysis. Since many experimental procedures use numerous probes to obtain statistically relevant data and/or to analyze multiple analytes for comparison, contamination opportunities increase accordingly.
Furthermore, manual handling of individual probes substantially reduces throughput when multiple individual probes are desired to be analyzed.
In addition, because some mass spectrometers accept only one probe at a time, the operator must be present to exchange individual probes if the operator desires to analyze a plurality of probes.
Some known MS systems have attempted to increase throughput and reduce the need for operator presence during MS analysis by automating insertion and removal of sample carriers into and out of mass spectrometers. One example system is described in U.S. Reissue Pat. No. RE37,485, which shows a single sample cassette or magazine within which a plurality of sample carriers may be removably carried to await analysis.
Additional examples of MS systems that comprise only a single sample cassette or magazine are described in U.S. Pat. Nos. 4,405,860; 4,879,458 and 4,076,982. Those systems appear to require the operator to manually load the sample carriers into their respective sample magazine or cassette. While the semi-automation reduces the need for constant operator presence during actual analysis, there still remains the need for the operator to manually load the sample carriers into the sample cassette prior to analysis. Thus, the number of manual operations and contamination opportunities remain high.
These problems discussed above are characteristic not only of MS systems, but of many applications that require an operator to load sample probes into an analytical instrument.
Thus, it would be desirable to provide a device for automating transfer of multiple sample probes between a cassette within which the plurality of probes are initially constrained and an analytical instrument that would reduce the opportunities for accidental operator contamination of the samples.
It would also be desirable to provide a device for automating transfer of multiple sample probes between a cassette within which the plurality of probes are initially constrained and an analytical instrument that would reduce the number of manual operations performed by an operator.
It further would be desirable to provide a device for automating transfer of multiple sample probes between a cassette within which the plurality of probes are initially constrained and an analytical instrument that would permit continuous analysis of a plurality of sample probes.
It still further would be desirable to provide a device for automating transfer of multiple sample probes between a cassette within which the plurality of probes are initially constrained and an analytical instrument that would reduce, if not eliminate, the necessity for constant operator surveillance during analysis of the plurality of sample probes.